The metabolism, placental transfer, and mechanism of action of some teratogens that affect the oral-facial region and skeletal system are under investigation. Studies with norchlorcyclizine, the major teratogenic metabolite of chlorcyclizine, have shown that it induces clefts of the secondary palate and limb anomalies in developing rat embryos and cartilage abnormalities in neonatal mice. Biochemical characterization of the cleft palate lesion have shown an acceleration of glycosaminoglycan degradation. The mechanism for this is being investigated using cell culture and cell-free systems. Animal models, including rodents, rabbits, and the subhuman primate, are being developed to evaluate normal and abnormal primary and secondary palate formation. For this purpose drugs of known and unknown mechanisms are being used. These include cyclophosphamide and diphenylhydantoin.